Plant ingredients in Thai food: a well-rounded diet for natural bioactive associated with medicinal properties

Background Seeking cures for chronic inflammation-associated diseases and infectious diseases caused by critical human pathogens is challenging and time-consuming. Even as the research community searches for novel bioactive agents, consuming a healthy diet with functional ability might be an effective way to delay and prevent the progression of severe health conditions. Many plant ingredients in Thai food are considered medicinal, and these vegetables, herbs, and spices collectively possess multiple biological and pharmacological activities, such as anti-inflammatory, antimicrobial, antidiabetic, antipyretic, anticancer, hepatoprotective, and cardioprotective effects. Methodology In this review, the selected edible plants are unspecific to Thai food, but our unique blend of recipes and preparation techniques make traditional Thai food healthy and functional. We searched three electronic databases: PUBMED, Science Direct, and Google Scholar, using the specific keywords “Plant name” followed by “Anti-inflammatory” or “Antibacterial” or “Antiviral” and focusing on articles published between 2017 and 2021. Results Our selection of 69 edible and medicinal plant species (33 families) is the most comprehensive compilation of Thai food sources demonstrating biological activities to date. Focusing on articles published between 2017 and 2021, we identified a total of 245 scientific articles that have reported main compounds, traditional uses, and pharmacological and biological activities from plant parts of the selected species. Conclusions Evidence indicates that the selected plants contain bioactive compounds responsible for anti-inflammatory, antibacterial, and antiviral properties, suggesting these plants as potential sources for bioactive agents and suitable for consumption for health benefits.


INTRODUCTION
Since the pandemic of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) began in 2019, searching for new potential antiviral agents and prophylactics has driven priorities in public health research and the scientific community. Furthermore, treatment many of these plants have also been used in traditional medicine over generations to maintain health or relieve and cure ailments and infectious diseases. With the increasing problems posed by antimicrobial resistance, viral diseases, and inflammatory conditions related to various symptoms and diseases, the ingredients and medicinal plants in Thai dishes could comprise a valuable potential resource for the discovery of bioactive compounds with anti-infective and protective effects.
Here, we highlight different plant species and parts used in Thai food and traditional medicine simultaneously, as part of a functional diet and as phytomedicine; we also discuss their important metabolites, therapeutic uses, and biological and pharmacological activities. Furthermore, this review summarizes an update of recent research papers on plant extracts and, in some instances, isolated compounds that have demonstrated anti-inflammatory effects and antibacterial activity against selected critical antibiotic-resistant bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) or antiviral activity against clinically significant human viruses such as influenza virus, herpes simplex virus, Zika virus, and SARS-CoV-2.
The present review provides an easy-to-access list of edible and medicinal plants as a database, which is vital in developing further applications in clinical practice and drug discovery to comply with the UN goal of sustainable development to promote good health and well-being. Moreover, these plants might be integrated into food processing and manufacturing or added into any diet regimen as ingredients that promote and restore health. Our review can guide further research and offers highly interesting material for other scientists working on several aspects of plant-related life sciences, natural products, and the international plant science community. Thai food is complex, and its plant ingredients are abundant in tropical and subtropical regions; that is, the plants discussed here are not specific to the South-East Asia region. To the best of our knowledge, our work represents one of the most comprehensive indexes of diverse plants from a single cuisine that feature bioactivities that impact human health. It can inform and increase public awareness about the importance of ongoing research activities in plant science, phytochemistry, and pharmacognosy.

SURVEY METHODOLOGY
For the development of this review, globally-recognized names of the plant materials selected based on their use in Thai food and folk medicine were obtained from Plants of the World Online (POWO; https://powo.science.kew.org/) and the International Plant Names Index (IPNI; https://www.ipni.org/). Related literature dated from 2017 to 2021 was then sourced from scientific databases including PUBMED, Science Direct, and Google Scholar by searching with the term "Plant name" followed by the keyword "Anti-inflammatory" or "Antibacterial" or "Antiviral." After carefully considering the obtained literature, we took only those publications that fit our scope of review. We proceeded to develop our database and produce this review. The compiled plant species and associated phytochemicals presented here have demonstrated the most promising health benefits and advantages with regard to targeting lead compounds.

AN OVERVIEW OF CULINARY HERBS, SPICES, AND MEDICINAL PLANTS IN THAI FOOD
We summarized a selection of 69 species (33 families) from edible and medicinal plants used in Thai food, and also Zingiber cassumunar in the family Zingiberaceae. The selection covers plant parts consumed as vegetables or as ingredients in the preparation of many Thai dishes. Based on several phytochemical studies, all of the selected plant species are potential sources of bioactive compounds in various classes; Table 1 presents the main chemical compositions of the different plant families and genera.
Many compound classes have been screened and identified in the plant species reviewed here and found to possess various medicinal properties. For example, essential oils or volatile oils, which mainly contain terpenes and terpenoids that are known as antioxidant, antimicrobial, anti-inflammatory, antidiabetic, anticancer, and antiallergic compounds, are found in aromatic plants belonging to the families Apiaceae, Clusiaceae, Lamiaceae, Lauraceae, Myristicaceae, Myrtaceae, Rutaceae, and Zingiberaceae (Marrelli et al., 2020;Masyita et al., 2022). Likewise, the alkaloid piperine and its derivatives are found in plants of the family Piperaceae and have several documented biological activities (Tiwari, Mahadik & Gabhe, 2020). Other major classes of phenolic compounds include polyphenols, phenolic acids, flavonoids, tannins, stilbenes, lignins, lignans, and coumarins, which have shown anti-inflammatory, anti-infective, antiproliferative, and antioxidant activities (Luna-Guevara et al., 2018). Curcuminoids are another group of polyphenols found in Curcuma species of the family Zingiberaceae that have been reported as having antioxidant, anti-inflammatory, antimutagenic, antimicrobial, and anticancer properties (Hewlings & Kalman, 2017). Meanwhile, natural xanthones are an important class of compounds in Garcinia species of the family Clusiaceae that have potential for treating inflammatory skin diseases (Gunter et al., 2020). Notably, xanthones are also found in the root part of Cratoxylum formosum in the family Hyperiaceae (Table 1). Hence, non-edible parts of plants should be evaluated for their potential as additional sources of new bioactive compounds (Svobodova et al., 2017;Rodanant et al., 2017;Maduka & Ikpa, 2021). Among the 69 plant species reviewed here, the commercially used species have been thoroughly investigated for constituent bioactive substances (Jantan et al., 2019;Oyeyinka & Afolayan, 2020;Marefati et al., 2021;Sari, Bellatasie & Ifora, 2021). However, there is very little literature on some less-widely used plant species, such as Telosma cordata in the family Apocynaceae (Nguyen, 2020).
Individual plants that are also used in traditional medicine and have shown various pharmacological properties are listed in Table 2. The claimed traditional uses of the selected plants are supported by updated documentation of their pharmacological activities, including antioxidant, antimicrobial, anti-inflammatory, hypolipidemic, antihypertension, antidiabetic, and other like health benefits. In some cases, it is unclear which part of the plant is used to obtain the mentioned therapeutic effect, and there is yet insufficient comparative study of phytochemical and biological activity in different parts of a given plant species. Content of bioactive compounds might vary in different parts of the same plant and in plants of closely related genera (Buathong et al., 2019). Thus, comprehensive studies of the chemical composition and bioactive components in different plant parts and in other genera that have closed taxonomic relationships with the plants listed in this work will open more possibilities for the discovery of new sources and active compounds and hence the expansion of phytomedicine development.       Inflammation is divided into two types: acute and chronic. Acute inflammation is a defense mechanism induced in response to harmful stimuli such as infections, injuries, and chemicals and is recognized by swelling, redness, fever, and pain. Chronic inflammation will occur if acute inflammation lingers for a long time, eventually leading to oxidative stress-mediated diseases, heart disease, diabetes, cancer, arthritis, and bowel diseases like ulcerative colitis (Marefati et al., 2021). Infectious diseases caused by microorganisms and pathogenic viruses can also induce cellular responses, activating signaling molecules such as NO and ROS that contribute to the inflammatory process by triggering the release of a cytokine storm that includes pro-inflammatory cytokines like TNF-a and interleukin (IL-1β, IL-6); this results in cell death (apoptosis) that can lead to acute respiratory distress or syndrome (ARDS), as seen after infection with SARS-CoV-2 (Donma & Donma, 2020).
In this regard, we provide a recent backdated review to update the field on the discovery of many extracts and isolated compounds from plant species, with a specific focus on anti-inflammatory properties observed upon administration in study models and on antimicrobial effects demonstrated against antibiotic-resistant bacteria and clinically significant viruses.

Anti-inflammatory activity
Many researchers and scientists have attempted to demonstrate the potential of selected plants as bioactive anti-inflammatory agents; this activity is assessed by decreasing and inhibiting different mediators and pathways, and by microscopic changes. Among the selected species, a total of 49 species in 24 families have recently been investigated for their anti-inflammatory effects through in vitro and in vivo experimental studies (Table 3). Crude extracts, fractions, juice, and isolated compounds of Thai food plant ingredients have all demonstrated the potential to complement searches for anti-inflammatory drugs.
Reports of bioactivity have also been published for gel, ointment, and patch formulations, and for co-treatment with selected plants (Table 3). In one case, a concoction of Coriandrum sativum (Apiaceae) with Coscinium fenestratum showed potent in vivo anti-inflammatory activity (Kothalawala et al., 2020). Anti-inflammatory effects with potential in product development have also been exhibited by essential oil from Syzygium aromaticum (Myrtaceae) formulated in an absorption base ointment with added oleic and propylene glycol (Sugihartini et al., 2019), a leaf patch from Sauropus androgynus (Phyllanthaceae) (Desnita et al., 2018), and a gel containing encapsulated niosomes of Plai oil (Z. cassumunar, Zingiberaceae) (Leelarungrayub, Manorsoi & Manorsoi, 2017). Finally, co-treatment using Curcuma longa (Zingiberaceae) and Allium hookeri extracts at a ratio of 3:7 showed optimal anti-inflammatory properties, indicating a synergistic plant-plant combination effect (Lee et al., 2020).
However, there still remains a need to establish a direct link between a plant extract and its putative bioactive compounds, for example flavonoids and essential oils, to further elucidate the anti-inflammatory role and help design clinical research and address the current insufficient body of evidence. This will allow developing a better understanding and implementation that might promote health maintenance and prevent numerous health conditions and diseases related to the inflammatory response.

Antibacterial
Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae have been listed as antibiotic-resistant bacteria by the World Health Organization (WHO) since 2017. Of those, P. aeruginosa (carbapenem-resistant) and Enterobacteriaceae like K. pneumoniae and E. coli (carbapenem-resistant) can produce extended-spectrum beta-lactamases (ESBLs) to interfere with beta-lactam antibiotics, and are accordingly ranked as of the utmost priority, followed by S. aureus (methicillinresistant and vancomycin-intermediate and -resistant) (Magryś, Olender & Tchórzewska, 2021). Moreover, as noted in a previous systematic review article, these bacteria have been ranked as the top four targeted pathogenic bacteria for a decade, indicating the ongoing need to combat their antibiotic-resistant strains (Chassagne et al., 2021). The authors also pointed out in that review that among the 15 most represented plant families, those most reported as having antibacterial activities are Lamiaceae, Fabaceae, and Asteraceae.
In many cases, the antibacterial activity of a plant extract may be ascribed to predominant essential oils, such as in an essential oil extract of Ocimum gratissimum   (Srifuengfung et al., 2020). Other classes of compounds also function as bioactive antibacterial agents, as demonstrated for the phenylbutanoid (E)-3-(3,4dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl] cyclohex-1-ene isolated from Z. cassumunar (Zingiberaceae), which showed high antibacterial activity against S. aureus and E. coli with MIC values of 16 mg/mL (Taechowisan, Suttichokthanakorn & Phutdhawong, 2018), while also having only weak cytotoxic activity. These findings support that many plant ingredients in Thai food can be taken as supplements for restoring health and can serve as powerful resources for developing antibiotic agents to treat serious and common infectious diseases.

Antiviral activities
Given the pandemic situation for the past few years, new and effective antiviral agents are needed for the development of vaccines and drugs. Currently available synthetic drugs may have adverse effects or cause drug resistance to nucleoside analogs via mutation (Mohan et al., 2020b). For these reasons, plant sources and phytomedicine have gained much interest in relation to antiviral drug discovery. Edible and medicinal plants are a powerful source of bioactive compounds and advantageous in terms of safety. Among the 69 plant species covered here, a few have been well-studied with regard to constituent phytochemicals and have demonstrated broad antiviral activities; these include Allium sativum (Amaryllidaceae) (Rouf et al., 2020) and Curcuma longa (Zingiberaceae) (Praditya  (Parham et al., 2020). In the current review, we give an update on 17 plant species (12 families) recently published for their antiviral activity against some human viruses (Table 5). In particular, several studies have demonstrated effectiveness of plant extracts and, in some cases, isolated compounds against important  Adamu et al., 2020) and Piper nigrum (Piperaceae) (Priya & Kumari, 2017;Nag & Chowdhury, 2020) are of particular interest as they have shown a vaster range of antiviral activities. In the case of Piper nigrum, this might be an effect of the bioactive alkaloid piperine or derivatives, which are known for antiviral effects against HSV and the flu virus (Mohan et al., 2020b), while the activity of Moringa oleifera may be attributable to isothiocyanate-1, which possess anti-inflammatory properties, or to other constituents (Jaja-Chimedza et al., 2017). Moreover, comparing plant species in Table 5 with Table 1 reveals 14 antiviral plants that have exhibited anti-inflammatory properties, suggesting a synergism between immunomodulatory effects and the inhibition of viral invasion or replication.
Remarkably, some plant species stand out based on their effectiveness at very low concentrations; these are Carica papaya (Caricaceae) (Haddad et al., 2020), Cissampelos pareira (Menispermaceae) (Ashraf et al., 2017), and B. rotunda (Zingiberaceae) (Kanjanasirirat et al., 2020), and the findings suggest sufficient specificity (extracts were used at concentrations of less than 10 µg/mL) that these might be good candidates for developing antiviral agents and merit further evaluation against a broader group of viruses. Particularly, B. rotunda extract and its isolated component panduratin A have promising antiviral activity against SARS-CoV-2 (COVID-19) (Kanjanasirirat et al., 2020). The authors found that infected Vero E6 cells were rapidly suppressed after treatment with extract or panduratin A, which had IC 50 values of 3.62 mg/mL (CC 50 = 28.06 mg/mL) and 0.81 mM (CC 50 = 14.71 mM), respectively. At the pre-entry phase, panduratin A inhibited SARS-CoV-2 infection with IC 50 of 5.30 mM (CC 50 = 43.47 mM). However, we have only summarized recent investigations of antiviral activity. Many more plant species on the list might also have potential as sources of antiviral agents, just waiting for other researchers to discover them.

CONCLUSIONS
Plants used as ingredients in Thai food are typically also medicinal plants with applications proven long ago in folk medicine. This review describes the great extent of available information on edible and medicinal plants and isolated molecules from Thai food sources, which until now has existed as scattered pieces of information that have never been combined. The plant list includes diverse families with therapeutic importance supported by the various pharmacological activities, significant bioactive metabolites, and updated anti-inflammatory, antibacterial, and antiviral properties for which evidence has been collected in recent years. Based on the literature, plants used as ingredients in Thai food would be justified as elements of a healthy and functional diet and as sources of upand-coming drug candidates with lesser toxicity. Many plant species have dual activity, demonstrating both anti-inflammatory and antimicrobial effects towards antibiotic-resistant bacteria and clinically significant viruses. In addition, more than one plant species is generally used for a single dish, as in traditional medicine practice. Hence, the effect of plant-plant combinations should be evaluated so as to enhance health restoration, therapeutic effects, and the development of supplementation and pharmaceutical-related products.
In Thailand, Andrographis paniculata (Burm. f.) Wall. ex Nees or Fah Talai Jone, a plant that has been used to treat and relieve common cold symptoms for years, has been included in The National List of Essential Drugs since 1999 and has become of renewed interest because of the COVID-19 pandemic around the globe. Encapsulated powder or extract of Andrographis paniculata with its major component, andrographolide, taken as a dose of 180 mg per day for five consecutive days, was recommended by the department of medicinal services for patients with mild symptoms (Mahajaroensiri et al., 2021). Concerning toxicity, a recent research article indicated that Andrographis paniculata extract and andrographolide respectively had no toxicity and a favorable toxicity profile in six representative human cell lines from the liver, kidney, intestine, lung, and brain. Both extract and andrographolide possess anti-SARS-CoV-2 activity and should be further investigated for their bioavailability and development for clinical applications as a monotherapy or in combination with other drugs (Sa-Ngiamsuntorn et al., 2021). In addition to that exemplar, this review emphasizes a promising plant list that will be of help in encouraging further investigation into mechanisms, synergy with antibiotics, formulations, physicochemical properties, bioavailability, and clinical research for the practical utilization of bioactive plant products. Moreover, the current review shall aid in the better selection of plant parts and species and promote their evaluability as food ingredients, functional foods, beverages, dietary supplements, and herbal medicines to preserve and increase vitality, slow aging, and promote well-being.